A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors

Inclusion Criteria:

• Participant has provided informed consent/assent before initiation of any studyspecific activities/procedures.

• Age ≥ 18 years.

• Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null) (Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP) (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAPexpression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).

• Histologically confirmed metastatic or locally advanced solid tumor not amenable tocurative treatment with surgery and/or radiation.

• Able to swallow and retain orally (PO) administered study treatment and willing torecord daily adherence to investigational product.

• Disease measurable as defined by Response Evaluation Criteria in Solid TumorsVersion 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

• Adequate hematopoietic function per local laboratory

• Adequate renal function per local laboratory

• Adequate glucose control per local laboratory (Part 1 only)

• Adequate liver function per local laboratory

• Adequate coagulation parameters

• Adequate pulmonary function

• Adequate cardiac function

• Minimum life expectancy of 12 weeks as per investigator judgement.

• Archived tumor tissue (formalin-fixed, paraffin-embedded [FFPE] sample collectedwithin 5 years) or an archival block must be available.

• For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergotumor biopsy.

• For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained with 6 months of enrollment and subject hasnot received any other treatment since sample was obtained) and while on treatment.

• For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sitesonly).

Food Effect Substudy (Part 1k): Specific Inclusion Criteria

• Subject able and willing to eat a standardized high-fat, high-caloric meal

• Subject able and willing to fast for ≥ 6 hours

Specific Inclusion Criteria for subjects with glioma (Part 1m only)

• Disease measurable as defined per Modified Response Assessment in Neuro-OncologyCriteria 2.0 (mRANO 2.0)

Exclusion Criteria:

• Spinal cord compression or untreated brain metastases or leptomeningeal disease.

• History of other malignancy within the past 2 years

• Any evidence of current interstitial lung disease

• Active infection

• Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2)infection.

• History of arterial thrombosis

• Myocardial infarction and/or symptomatic congestive heart failure.

• Gastrointestinal tract disease

• History of bowel obstruction, abdominal fistula, gastrointestinal perforation, orintra-abdominal abscess

• History of solid organ transplant.

• Diagnosis of Congenital Short QT Syndrome.

• Major surgery

• Anti-tumor therapy within 28 days of study day 1.

• Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or aprotein arginine methyltransferase 5 (PRMT5) inhibitor.

• Prior treatment with docetaxel (Part 2 only)

• Prior irradiation to 25% of the bone marrow.

• Therapeutic or palliative radiation therapy within 2 weeks of study day 1.

• Live vaccine therapy within 4 weeks before study drug administration.

• Use of therapeutic anti-coagulation for treatment of active thromboembolic events.

• Use of prescription medications that are known strong inducers of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1

• Unresolved toxicity from prior anti-cancer therapy

• Currently receiving treatment in another investigational device or drug study.

• Known positive test for Human Immunodeficiency Virus (HIV).

• Positive hepatitis B surface antigen

• positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)

• Female participants of childbearing potential unwilling to use protocol specifiedmethod of contraception